Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal (GI) disorders worldwide. Defined as a disorder of gut-brain interaction, its pathophysiology is still not completely clear. Consequently, current treatments primarily target symptoms rather than addressing the cause of the condition. The gut microbiome is increasingly acknowledged as central to IBS pathophysiology and, thus, may have therapeutic potential. Several national treatment guidelines recommend increasing physical activity for IBS management.

This review summarises the evidence about the relationship between physical activity, IBS symptoms, and the gut microbiome, investigating the hypothesis that physical activity's therapeutic effects on IBS may be explained via modulation of the gut microbiome.

This review revealed that routine exercise was associated with a 15%-66% reduction in symptom severity and up to 41% enhanced QoL in IBS participants, and modulates the gut microbiome in healthy controls.

This review generates the hypothesis that routine physical activity may favorably alter gut microbiome composition in IBS to improve IBS symptomology. While a plausible hypothesis, research needs to confirm whether gut microbiome modulation is involved in physical activity associated IBS symptom relief.

Furthermore, the establishment of the most effective mode, duration, and intensity of physical activity for each sex and IBS-subtype is needed, with patient input during this process crucial to successfully translate science into practice.

Bidirectional communications between the gut and the brain play an important role in the regulation of food intake, pain perception, mood, and cognitive function. The involved communication pathways are modulated by signals generated by the gut microbiome. Alterations in these communications have been implicated in several chronic brain and gut disorders, including food addiction, mood disorders, neurodevelopmental and neurodegenerative disorders, and functional and inflammatory bowel disorders. The gut microbiome holds great promise for the development of novel therapies normalizing altered brain-gut interactions.

Obstructive sleep apnea (OSA), is associated with dysfunction in the cardiovascular, metabolic and neurological systems. However, the relationship between OSA and memory impairment, intervention effects, and underlying pathways are not well understood. This review summarizes recent advances in the clinical characterization, treatment strategies, and mechanisms of OSA-induced memory impairments. OSA patients may exhibit significant memory declines, including impairments in working memory from visual and verbal sources. The underlying mechanisms behind OSA-related memory impairment are complex and multifactorial with poorly understood aspects that require further investigation. Neuroinflammation, oxidative stress, neuronal damage, synaptic plasticity, and blood-brain barrier dysfunction, as observed under exposures to intermittent hypoxia and sleep fragmentation are likely contributors to learning and memory dysfunction. Continuous positive airway pressure treatment can provide remarkable relief from memory impairment in OSA patients. Other treatments are emerging but need to be rigorously evaluated for cognitive improvement. Clinically, reliable and objective diagnostic tools are necessary for accurate diagnosis and clinical characterization of cognitive impairments in OSA patients. The complex links between gut-brain axis, epigenetic landscape, genetic susceptibility, and OSA-induced memory impairments suggest new directions for research. Characterization of clinical phenotypic clusters can facilitate advances in precision medicine to predict and treat OSA-related memory deficits.

The urobiome, or urinary tract microbiome, has emerged as a crucial component in maintaining urinary health and defending against infections. Recent advances in next-generation sequencing (NGS) have debunked the long-held belief that the urinary tract is sterile, revealing a unique ecosystem of microorganisms. The urobiome interacts with the urothelium and mucosa-associated lymphoid tissue (MALT) to support local immunity, playing an integral role in defending the urinary tract against pathogens. Through complex communication processes like quorum sensing, the urobiome regulates microbial behavior and controls interactions with host tissues, helping to prevent pathogen colonization and infection. However, dysbiosis in the urobiome can disrupt this balance, making the urinary tract more susceptible to infections, including urinary tract infections (UTIs). Studies have highlighted specific microbial compositions associated with both healthy and disease states, suggesting that shifts in the urobiome may correlate with various urological diseases. Furthermore, microbial diversity within the urinary tract differs by factors such as age and gender, reflecting the dynamic nature of the urobiome. Future research focusing on the interplay between the urobiome, host immune defenses, and pathogenic mechanisms may lead to innovative diagnostic and therapeutic approaches. Understanding how microbial composition changes during disease states could enable targeted treatments, potentially reducing reliance on antibiotics and minimizing resistance issues. The urobiome thus represents a promising frontier in urology, with implications for enhancing urinary health and treating infections more effectively.

Genetic factors and an unfavorable intrauterine environment may contribute to the development of metabolic disorders in offspring later in life. The present study aims to investigate and compare the risks of pre-diabetes mellitus (pre-DM), type 2 diabetes mellitus (T2DM) and abnormal glucose tolerance in female and male offspring with early maternal menopausal age versus those with normal maternal menopausal age, later in life.

In this prospective population-based study, there were 1,516 females and 1,563 males with normal maternal menopausal age, as well as 213 females and 237 males with early maternal menopausal age. Unadjusted and adjusted cox regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between early maternal menopausal age with pre-DM, T2DM and abnormal glucose tolerance in offspring. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05.

The present study revealed a higher risk of pre-DM in female offspring with early maternal menopausal age compared to females with normal maternal menopausal age (unadjusted HR (95% CI): 1.42 (0.98, 2.05); P = 0.06 (marginal significant) and adjusted HR (95% CI): 1.47 (1.00, 2.16); P = 0.04). Additionally, a higher risk of abnormal glucose tolerance among female offspring with early maternal menopausal age in adjusted model was observed (HR (95% CI): 1.13 (0.99-1.29); P = 0.06, marginal significant). However, no significant differences were observed in the risks of developing pre-DM and abnormal glucose tolerance in male offspring with early maternal menopausal age compared to males with normal maternal menopausal age in both unadjusted and adjusted models. No significant difference was observed in the risk of T2DM in the offspring with early maternal menopausal age compared to offspring with normal maternal menopausal age.

This pioneering study, characterized by a long-term follow-up, demonstrated that early maternal menopausal age is associated with an increased risk of developing pre-DM in female offspring later in life. It may be advisable to implement screening for pre-DM and glucose metabolism disorders in these female offspring.

Not applicable.

Proton pump inhibitors (PPIs) are widely prescribed, but their link to migraine risk, especially in Asian populations, remains unclear. This longitudinal study aimed to answer the following question: Does PPI exposure show a dose-dependent risk of migraine, varying by subtype and PPI indication in an Asian population?

Using Taiwan's National Health Insurance Research Database (2000-15), we conducted a matched case-control study on PPI exposure. Adults prescribed PPIs for peptic ulcers, gastroesophageal reflux disease, or upper gastrointestinal bleeding were included, excluding those with prior migraines or incomplete data. Controls were matched 1:1 by age, sex, and residence. PPI exposure was measured in cumulative defined daily doses (cDDDs).

The study included 22 834 PPI users (11 417 cases, 11 417 controls) with a mean follow-up of 4.1 ± 3.3 years. The study population comprised 65.6% females and 34.4% males, with no significant sex difference (P = 1.000). Mean age was 47.27 ± 15.16 years in cases and 47.42 ± 15.14 years in controls (P = .444). The average interval from PPI initiation to migraine diagnosis was 2.4 ± 1.9 years. Compared with those with the lowest PPI exposure (cDDD ≤30), migraine risk progressively increases with greater cumulative exposure: cDDD 31-120 [aOR = 1.22, 95% confidence interval (CI) = 1.15-1.30], cDDD 121-365 (aOR = 1.42, 95% CI = 1.32-1.52), and cDDD >365 (aOR = 1.60, 95% CI = 1.41-1.80). This dose-dependent relationship was consistent across migraine subtypes and PPI indications.

This large-scale Asian population study revealed a significant dose-dependent association between PPI exposure and increased migraine risk, emphasizing the need for cautious prescribing and monitoring of migraine symptoms in long-term PPI users, particularly in Asian populations.

The estimation of postmortem submersion interval (PMSI) has always been an important scientific issue to be addressed in drowning cases. Traditional methods, such as corpse temperature analysis and the assessment of corpse surface corruption, have limitations and cannot meet the need for accurate estimation of the time of death in the mid to late stages. Biogenic amines, as small molecules produced by protein degradation after death, have a certain regularity in relation to PMSI. To further explore the possibility of utilizing polyamines to estimate PMSI, this experiment constructed a rat cadaver model in both laboratory constant-temperature water and natural water bodies. Furthermore, cadaverine and putrescine in the liver and skeletal muscle were detected at different PMSI using gas chromatography-mass spectrometry (GC-MS). Through statistical analysis, we have constructed eight sets of mathematical models for polyamines-PMSI estimation, and determined the applicable time range through derivative analysis. After evaluation the models, the error rate in inferring PMSI using the fitted equations was less than 30 % within 242 h. The models established in this study could accurately infer PMSI in the mid to late stages of the postmortem period, providing a feasible approach for the drowning forensic issue.

Neurodevelopment is a multifaceted and tightly regulated process essential for the formation, maturation, and functional specialization of the nervous system. It spans critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, and synaptic pruning, which collectively establish the foundation for cognitive, behavioral, and emotional functions. Metabolism serves as a cornerstone for neurodevelopment, providing the energy and substrates necessary for biosynthesis, signaling, and cellular activities.

Key metabolic pathways, including glycolysis, lipid metabolism, and amino acid metabolism, support processes such as cell proliferation, myelination, and neurotransmitter synthesis. Crucial signaling pathways, such as insulin, mTOR, and AMPK, further regulate neuronal growth, synaptic plasticity, and energy homeostasis. Dysregulation of these metabolic processes is linked to a spectrum of neurodevelopmental disorders, including autism spectrum disorders (ASDs), intellectual disabilities, and epilepsy.

This review investigates the intricate interplay between metabolic processes and neurodevelopment, elucidating the molecular mechanisms that govern brain development and the pathogenesis of neurodevelopmental disorders. Additionally, it highlights potential avenues for the development of innovative strategies aimed at enhancing brain health and function.

Cancer has long been associated with genetic and environmental factors, but recent studies reveal the important role of gut microbiota in its initiation and progression. Around 13% of cancers are linked to infectious agents, highlighting the need to identify the specific microorganisms involved. Gut microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune responses. Dysbiosis can lead to cancer, while certain probiotics and their metabolites may help reestablish micro-ecological balance and improve anti-tumor immune responses. Research into targeted approaches that enhance therapy with probiotics is promising. However, the effects of probiotics in humans are complex and not yet fully understood. Additionally, methods to counteract harmful bacteria are still in development. Early clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer treatments. Ongoing research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.

Obesity is recognized as a global epidemic that can result in changes in the human body and metabolism. Accumulating evidence indicates that gut microbiota (GM) can affect the development of obesity. The GM not only plays a crucial role in digesting and absorbing nutrients, but also in maintaining the overall health of the host. Dietary supplements such as non-starch polysaccharides are mainly fermented by the GM in the colon. Recent findings suggest that shaping the GM through the prebiotic function of non-starch polysaccharides may be a viable strategy against obesity. In this paper, the effects of non-starch polysaccharides on host health, together with their prebiotic function influencing the GM to control obesity via the gut-target organ axis, are reviewed. Potential perspectives of non-starch polysaccharides exhibiting anti-obesity effects via the gut-target organ axis are proposed for future research.

Gut microbiota play a critical role in mediating the bidirectional association between cancer and depression. Emerging evidence indicates that adjusting the dietary component intake can significantly alter gut microbiota composition, thereby influencing the host's metabolism and immune function. Changes in gut microbiota and their metabolites may represent key factors in preventing cancer-depression comorbidity.

English publications were searched in databases including the Web of Science, Scopus, and PubMed using a series of keywords: "cancer", "depression", "gut microbiota", "dietary components", and related terms, individually or in combination. The search focused on preclinical and clinical studies describing the regulatory effects of dietary component interventions.

This narrative review summarizes the associations among gut microbiota, cancer, and depression, and synthesizes current evidence on the modulatory effects and mechanisms of specific dietary component interventions, including dietary patterns, probiotics, prebiotics, and diet-derived phytochemicals, on gut microbiota. On the one hand, these interventions inhibit abnormal proliferation signals in the tumor microenvironment and enhance anticancer immune responses; on the other hand, they modulate neurotransmitter homeostasis, suppress neuroinflammation, and improve mood behaviors through the gut-brain axis interactions mediated by microbial metabolites.

The complex associations among cancer, depression, and gut microbiota require further clarification. Modulating gut microbiota composition through dietary components represents a novel therapeutic strategy for improving cancer-depression comorbidity. Regulated gut microbiota enhance immune homeostasis and intestinal barrier function, while their metabolites bidirectionally modulate one another via systemic circulation and the gut-brain axis, thereby improving both the tumor microenvironment and depressive-like behaviors in cancer patients while reducing the adverse effects of cancer.

The gut microbiome plays a vital role in human health, functioning as a metabolic organ that influences nutrient absorption and overall well-being. With growing evidence that dietary interventions can modulate the microbiome and improve health, this review examines whether healthcare systems should prioritize personalized microbiome-targeted therapies, such as probiotics, prebiotics, and microbiota transplants, over traditional pharmaceutical treatments for chronic diseases like obesity, diabetes, cardiovascular risk, and inflammatory conditions. A systematic review using Web of Science and Scopus databases was conducted, followed by a scientometric analysis. Key metabolic pathways, such as dietary fiber fermentation and short-chain fatty acid production, were explored, focusing on their impact on lipid and glucose metabolism. The interactions between microbial metabolites and the immune system were also investigated. Dietary interventions, including increased fiber and probiotic intake, show potential for addressing dysbiosis linked to conditions, such as type 2 diabetes, obesity, and autoimmune diseases. The review emphasizes the need to incorporate microbiome modulation strategies into clinical practice and research, calling for a multidisciplinary approach that integrates nutrition, microbiology, and biochemistry to better understand the gut microbiome's complex role in health.

Antibiotics in early life can promote adiposity via interactions with the gut microbiota, but they represent only one possible route of antimicrobial exposure. Dietary preservatives exhibit antimicrobial activity, contain chemical structures accessible to microbial enzymes, and may therefore similarly disrupt microbial contributions to metabolic development.

Here, we test the hypothesis that preservatives alter the gut microbiota with consequences for host metabolism.

We screened common dietary preservatives for in vitro and ex vivo activity against a panel of gut bacteria and whole fecal microbial communities, profiling outcomes via optical density measurements and 16S rDNA sequencing. We then exposed adult mice to diet-relevant doses of 4 preservatives [acetic acid, butylated hydroxyanisole (BHA), ethylenediaminetetraacetic acid (EDTA), and sodium sulfite] or ampicillin (positive control) for 7 d. Finally, we examined the effects of early-life EDTA and low-dose ampicillin exposure starting in gestation in a mouse model, tracking differences in growth and metabolism.

Preservatives altered microbial growth and community structure in vitro, ex vivo, and in vivo, but with compound-specific changes in gut microbiota composition distinct from those of ampicillin. Long-term EDTA exposure from gestation reduced calorie absorption and cecal acetate, resulting in 32% lower gains in body fat in females for a given food intake (±12% standard error, linear mixed effects model). Females exposed to ampicillin exhibited a similar 42% (±11%) reduction in food-adjusted gains in adiposity, along with larger brains and smaller livers. By contrast, among males, EDTA had no detectable metabolic impacts whereas ampicillin exposure increased food-adjusted gain in body fat by 108% (±12%).

Our results highlight the potential for everyday doses of common preservatives to affect the gut microbiota and impact metabolism differently in males and females. Thus, despite their generally regarded as safe designation, preservatives could have unintended consequences for consumer health via their impact on the gut microbiota.

Emerging evidence indicates that inflammatory bowel disease (IBD) and dementia may share underlying pathological mechanisms and risk factors. However, the association between a prior IBD diagnosis and the subsequent risk of dementia remains largely unexplored. We conducted a comprehensive search of PubMed, Embase, and the Cochrane Library up to February 4, 2025, without language restrictions. Two reviewers independently extracted data and evaluated methodological quality and risk of bias. Observational studies comparing dementia risk in IBD and non-IBD populations were included. Pooled effect estimates for odds ratios (OR) were calculated using random-effects models. A total of 10 population-based studies, involving 7,895,339 participants (269,387 with IBD), were included. Meta-analysis of eight studies showed a significant association between IBD and dementia risk (OR 1.17, 95% CI: 1.08-1.27, P = 0.0001). However, IBD was not associated with an increased risk of Alzheimer's disease (AD) (OR 1.15, 95% CI: 0.98-1.36, P = 0.09). Stratified analysis by IBD type revealed a positive association between both ulcerative colitis (UC) and Crohn's disease (CD) and dementia risk (UC: OR 1.15, 95% CI: 1.05-1.25, P = 0.002, I² = 81%; CD: OR 1.26, 95% CI: 1.11-1.43, P = 0.0003, I² = 53%). This study identifies a significant correlation between IBD and dementia, suggesting that IBD patients have an elevated risk of developing dementia. However, current evidence is insufficient to establish a causal relationship. Further research should explore whether effective IBD treatments can mitigate this risk and elucidate the underlying pathophysiological mechanisms connecting these conditions.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation and significantly impairs quality of life through anxiety-like behaviors and visceral pain. Early evaluation of the risk of anxiety-like behaviors and visceral pain in IBD patients, along with targeted treatment, may benefit disease management. Visceral pain and anxiety-like behavior are often accompanied by neurological damage. Previous studies have shown that abnormal accumulation of glutamate can cause excitatory neurotoxic effects, leading to central nervous system (CNS) damage. Excitatory amino acid transporters (EAATs), particularly EAAT2, are known to regulate glutamate levels. The impact of hippocampal EAAT2 modulation on these clinical features in IBD is yet to be evaluated. Therefore, we designed this experiment to test this hypothesis. This study aimed to investigate the impact of altered levels of hippocampal EAAT2 on anxiety-like behaviors and visceral pain in mice with IBD. We observed reduced EAAT2 expression, increased glutamate levels, elevated N-methyl-d-aspartate receptors (NMDAR) expression, and obvious glutamate toxicity in the hippocampus of dextran sulfate sodium (DSS) induced IBD model mice. These mice exhibited significant visceral pain and anxiety-like behaviors. In summary, the reduced expression of EAAT2 in the hippocampus of individuals with IBD leads to elevated glutamate levels, resulting in neuronal damage and ultimately contributing to visceral pain and anxiety-like behaviors. These findings suggest that EAAT2 could serve as a therapeutic target for neurologically derived IBD symptoms.

The gut-brain axis (GBA) is involved in the modulation of multiple physiological activities, and the vagus nerve plays an important role in this process. However, the association between vagus nerve function and nutritional regulation remains unclear. Here, we explored changes in the nutritional status of mice after vagotomy and investigated the underlying mechanisms responsible for these changes.

We performed vagotomies in mice and verified nerve resection using immunofluorescence staining. We then observed the food intake and body weight of the mice and tested nutritional and inflammation-related markers using enzyme-linked immunosorbent assay (ELISA) kits. The role of glucagon-like peptide 1 (GLP-1) in the GBA was determined using qRT-PCR and ELISA kits. Western blot and ELISA kits were used to explore the underlying mechanisms.

After vagotomy, the mice experienced a deterioration in their nutritional status, which manifested as a significant reduction in body weight and food intake. The expression of the proglucagon gene (GCG), which encodes GLP-1, significantly increased after vagotomy. Mechanistically, acetylcholine (ACh) reversed the HG (high glucose) -induced elevation of GLP-1 secretion. ACh upregulated AMPKα phosphorylation, thereby reducing GLP-1 secretion. Moreover, the level of AMPKα phosphorylation was enhanced by ACh via M3AChR.

ACh released by the vagus nerve counteracts the anorectic effects of GLP-1 under normal physiological conditions. Vagotomy blocks this feedback, resulting in a loss of food intake and body weight in mice.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Prolonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants. Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk. However, the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis. This study recruited 109 young male migrants living in Xizang to investigate the microbial mechanisms underlying cognitive impairment associated with high-altitude migration. Multi-omic analysis revealed distinct microbiome and metabolome features in migrants with cognitive decline, notably a reduced abundance of Clostridium species and disrupted fecal absorption of L-valine. Mechanistic studies showed that hypobaric hypoxia significantly damaged the intestinal barrier, leading to lipopolysaccharide (LPS) leakage and an influx of inflammatory factors into the peripheral blood, which activated microglia and caused neuronal injury in the hippocampus of mice. Additionally, compromised L-valine absorption due to intestinal barrier damage correlated with lower hippocampal glutamate levels and neurotrophic factors. Intervention with Clostridium sp. effectively restored the intestinal barrier and enhanced L-valine absorption, which mitigated hypobaric hypoxia-induced inflammation and hippocampal neural damage in mice. In conclusion, cognitive impairment among young migrants at high altitude may be attributed to hypobaric hypoxia-induced gut microbiota disruption and subsequent intestinal barrier dysfunction. This study may provide a promising approach for preventing and treating high-altitude-associated cognitive impairment.

The appendix, an integral part of the large intestine, may serve two purposes. First of all, it is a concentration of lymphoid tissue that resembles Peyer's patches. It is also the main location in the body for the creation of immunoglobulin A (IgA), which is essential for controlling intestinal flora's density and quality. Second, the appendix constitutes a special place for commensal bacteria in the body because of its location and form. Inflammation of the appendix, brought on by a variety of infectious agents, including bacteria, viruses, or parasites, is known as appendicitis. According to a number of studies, the consequences of appendectomies may be more subtle, and may relate to the emergence of heart disease, inflammatory bowel disease (IBD), and Parkinson's disease (PD), among other unexpected illnesses. A poorer prognosis for recurrent Clostridium difficile infection is also predicted by the absence of an appendix. Appendectomies result in gut dysbiosis, which consequently causes different disease outcomes. In this review, we compared the compositional differences between the appendix and gut microbiome, the immunological role of appendix and appendix microbiome (AM), and discussed how appendectomy is linked to different disease consequences.

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain-gut-microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain-gut-microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain-gut-microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain-gut-microbiome axis.

Significance: Hydrogen sulfide (H2S), a ubiquitous small gaseous signaling molecule, plays a critical role in various diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ischemic stroke, and myocardial infarction (MI) via reducing inflammation, inhibiting oxidative stress, and cell apoptosis. Recent Advances: Uncontrolled inflammation is closely related to pathological process of ischemic stroke, RA, MI, and IBD. Solid evidence has revealed the axes between gut and other organs like joint, brain, and heart, and indicated that H2S-mediated anti-inflammatory effect against IBD, RA, MI, and ischemic stroke might be related to regulating the functions of axes between gut and other organs. Critical Issues: We reviewed endogenous H2S biogenesis and the H2S-releasing donors, and revealed the anti-inflammatory effects of H2S in IBD, ischemic stroke, RA, and MI. Importantly, this review outlined the potential role of H2S in the gut-joint axis, gut-brain axis, and gut-heart axis as a gasotransmitter. Future Direction: The rate, location, and timing of H2S release from its donors determine its potential success or failure as a useful therapeutic agent and should be focused on in the future research. Therefore, there is still a need to explore internal and external sources monitoring and controlling H2S concentration. Moreover, more efficient H2S-releasing compounds are needed; a better understanding of their chemistry and properties should be further developed. Antioxid. Redox Signal. 42, 341-360.

The human immune system is closely linked to microbiota such as a complex symbiotic relationship during the coevolution of vertebrates and microorganisms. The transfer of microorganisms from the mother's microbiota to the newborn begins before birth during gestation and is considered the initial phase of the intestinal microbiota (IM). The gut is an important site where microorganisms can establish colonies. The IM contains polymicrobial communities, which show complex interactions with diet and host immunity. The tendency towards dysbiosis of the intestinal microbiota is influenced by local but also extra-intestinal factors such as inflammatory processes, infections, or a septic state that can aggravate it. Pathogens could trigger an immune response, such as proinflammatory responses. In addition, changes in the host immune system also influence the intestinal community and structure with additional translocation of pathogenic and non-pathogenic bacteria. Finally, local intestinal inflammation has been found to be an important factor in the growth of pathogenic microorganisms, particularly in its role in sepsis. The aim of this article is to be able to detect the current knowledge of the mechanisms that can lead to dysbiosis of the intestinal microbiota and that can cause bacterial translocation with a risk of infection or septic state and vice versa.

Perioperative cognitive dysfunction is a common complication in stroke patients undergoing secondary surgeries. This study investigated the effects of tibial fracture internal fixation (TFIF) surgery on cognitive function and the gut microbiota in mice with a history of stroke. Using the middle cerebral artery occlusion method to induce stroke, we assessed cognitive function via the fear conditioning test and analyzed the gut microbiota through 16S rRNA sequencing. Compared with those in the normal and stroke groups, the cognitive function of the mice in the stroke group that underwent TFIF surgery was significantly impaired. Gut microbiota analysis revealed significant changes in beta diversity, but not in alpha diversity, in these mice. Additionally, TFIF surgery increased microglial activation and IL-1β and lipopolysaccharide (LPS) levels in the brain while reducing α-defensin levels and increasing IL-1β and LPS levels in the colon. These results suggest that TFIF surgery exacerbates cognitive impairment in stroke mice, possibly through alterations in the gut microbiota that impair intestinal defense and promote inflammation. This study highlights the critical role of the gut microbiome in cognitive function and perioperative outcomes, offering insights into potential therapeutic strategies for perioperative cognitive dysfunction in stroke patients.

Human longevity is a sex-biased process in which sex chromosomes and sex-specific immunity may play a crucial role in the health and lifespan disparities between men and women. Generally, women have a higher life expectancy than men, exhibiting lower infection rates for a broad range of pathogens, which results in a higher prevalence of female centenarians compared to males. Investigation of the immunological changes that occur during the process of healthy aging, while taking into account the differences between sexes, can significantly enhance our understanding of the mechanisms that underlie longevity. In this review, we aim to summarize the current knowledge on sexual dimorphism in the human immune system and gut microbiome during aging, with a particular focus on centenarians, based exclusively on human data.

Fungicides have been increasingly used across various sectors, including agriculture and textiles. The biocidal properties of fungicides may negatively impact the stability of intestinal microbiota, thereby posing a threat to intestinal health. In this study, we investigated the mechanisms of intestinal damage and functional abnormalities in grass carp following a 42-day exposure to the widely used fungicide carbendazim at environmentally relevant concentrations (0.2 to 20 μg/L). Histopathological observations, mRNA and protein expression analyses, biochemical analysis, quantification of short-chain fatty acids (SCFAs), cytokines, lipopolysaccharide (LPS), and 16S ribosomal ribonucleic acid (rRNA), as well as internal transcribed spacer (ITS) sequencing, were performed. At environmentally relevant concentrations, carbendazim strongly induced intestinal inflammation, leading to increased transcriptional and translational levels of genes involved in the toll-like receptor five (TLR5)/nuclear factor kappa B (NF-κB) pathway, including TLR5, NF-κB, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNFα). Additionally, carbendazim damaged intestinal barriers and reduced the expression of tight junction proteins (e.g., occludin and zonula occludens-1/2), goblet cells, and immunoglobulin M levels, while also disrupting the gut microbiome, leading to intestinal metabolic disorders, particularly decreases in SCFAs and increases in LPS. Treatment with the TLR5 antagonist TH1020 mitigated intestinal inflammation caused by carbendazim, subsequently improving mechanical barrier function. Overall, our findings provide new insights into the toxicological mechanisms underlying intestinal damage caused by carbendazim in grass carp, indicating that carbendazim poses a significant threat to nontarget organisms. Given its widespread detection in the environment, these results underscore the substantial ecological risks to the gut health of fish living in carbendazim-contaminated water bodies.

The gut microbiota is known to interact with various organs in the body, including the central nervous system, through the gut-brain axis. Intestinal dysbiosis can lead to increased peripheral inflammation and, consequently, affect the brain, resulting in neuroinflammation. Photobiomodulation (PBM) has demonstrated positive regulatory effects on the imbalance of certain body functions, including pain, inflammation, immunity, wound healing, and gut microbiota dysbiosis. Therefore, PBM at the intestinal level could help improve intestinal dysbiosis and reestablish cerebral homeostasis. In this context, this study aimed to conduct a narrative review of the literature on the effects of PBM at the intestinal level on intestinal dysbiosis and neuroinflammation. Overall, the findings highlight that PBM modulates the gut microbiota, suggesting it could serve as a therapy for neurological conditions affecting the gut-brain axis. Future research should focus on further elucidating the molecular mechanisms underlying this therapy.

Prebiotic dietary fiber (PDF) may reduce feelings of stress or improve mood in healthy individuals. Yet gut intervention studies that focus on mood in daily life are lacking and few studies include extensive biological sample analyses to gain mechanistic insights. As part of a larger randomized placebo-controlled crossover study including healthy individuals, we explored the effects of 12 weeks of PDF (acacia gum and carrot powder) on everyday mood, as measured with ecological momentary assessment (EMA). Microbiome composition and levels of microbial metabolites, endocrine, and inflammatory markers were determined prior to and after both intervention phases. Fifty-four participants completed the study. The intervention significantly increased daily positive affect (PA) and reduced daily negative affect (NA) in female but not male participants. The intervention-induced reduction in NA was associated with an increase in microbial diversity in female participants. The intervention did not significantly affect levels of fecal short chain fatty acids, cortisol, and inflammatory markers. This is one of the first studies to show that a dietary fiber intervention can positively alter mood as it is experienced in everyday life. Overall, our findings may stimulate more targeted gut-microbiome interventions and detection of its mental health effects in real life.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by motor symptoms and non-motor symptoms. It has been found that intestinal issues usually precede motor symptoms. Microorganisms in the gastrointestinal tract can affect central nervous system through the microbiota-gut-brain axis. Accumulating evidence has shown that disturbances in the microbiota-gut-brain axis are linked with PD. Thus, this pathway appears to be a promising therapeutic target for treatment of PD.

In this review, we mainly described gut dysbiosis in PD and their underlying mechanisms for mediating neuroinflammation and peripheral immune response in PD pathology and futher discussed the potential small-molecule compounds and genic therapeutic strategies targeting the microbiota-gut-brain axis and their applications in PD.

Studies have found that some small molecule compounds and alterations of inflammation-related genes can improve the motor and non-motor symptoms of PD by improving the microbiota-gut-brain axis, which may provide potentially beneficial drugs and molecular targets for the therapies of PD.

The gut microbiome is a complex system that directly interacts with and influences many systems in the body. This delicate balance of microbiota plays an important role in health and disease and is highly influenced by lifestyle factors and the surrounding environment. As further research emerges, understanding the full potential of the gut microbiome and the impact of using nutraceuticals to positively influence its function may open the door to greater therapeutic outcomes in the treatment and prevention of disease. Curcumin, a bioactive compound derived from the turmeric rhizome, has been studied in depth for its influence on human health as a potent anti-inflammatory and antioxidant properties. However, the therapeutic activity of curcumin is limited by its low oral bioavailability. While most available research has primarily focused on the curcuminoid compounds of turmeric, the non-curcuminoid compounds hold promise to offer therapeutic benefits while synergistically enhancing the bioavailability of curcumin and supporting the gut microbiome. This review summarizes current knowledge of the relationship between the gut and the various systems within the body, and how dysbiosis, or disruption in the gut microbial balance, leads to inflammation and increased risk of chronic disease. The review also summarizes recent research that focuses on the bioactivity of both the curcuminoid and non-curcuminoid compounds that comprise the whole turmeric root and their synergistic role in enhancing bioavailability to support a healthy gut microbiome and promising use in the treatment and prevention of disease.

Among living organisms, higher animals primarily use a combination of vocal and non-verbal cues for communication. In other species, however, chemical signaling holds a central role. The chemical and biological activity of the molecules produced by the organisms themselves and the existence of receptors/targeting sites that allow recognition of such molecules leads to various forms of responses by the producer and recipient organisms and is a fundamental principle of such communication. Chemical language can be used to coordinate processes within one species or between species. Chemical signals are thus information for other organisms, potentially inducing modification of their behavior. Additionally, this conversation is influenced by the external environment in which organisms are found. This review presents examples of chemical communication among microorganisms, between microorganisms and plants, and between microorganisms and animals. The mechanisms and physiological importance of this communication are described. Chemical interactions can be both cooperative and antagonistic. Microbial chemical signals usually ensure the formation of the most advantageous population phenotype or the disadvantage of a competitive species in the environment. Between microorganisms and plants, we find symbiotic (e.g., in the root system) and parasitic relationships. Similarly, mutually beneficial relationships are established between microorganisms and animals (e.g., gastrointestinal tract), but microorganisms also invade and disrupt the immune and nervous systems of animals.

Despite offering significant conveniences, plastic materials contribute substantially in developing environmental hazards and pollutants. Plastic trash that has not been adequately managed may eventually break down into fragments caused by human or ecological factors. Arguably, the crucial element for determining the biological toxicities of plastics are micro/nano-forms of plastics (MPs/NPs), which infiltrate the mammalian tissue through different media and routes. Infiltration of MPs/NPs across the intestinal barrier leads to microbial architectural dysfunction, which further modulates the population of gastrointestinal microbes. Thereby, it triggers inflammatory mediators (e.g., IL-1α/β, TNF-α, and IFN-γ) by activating specific receptors located in the gut barrier. Mounting evidence indicates that MPs/NPs disrupt host pathophysiological function through modification of junctional proteins and effector cells. Moreover, the alteration of microbial diversity by MPs/NPs causes the breakdown of the blood-brain barrier and translocation of metabolites (e.g., SCFAs, LPS) through the vagus nerve. Potent penetration affects the neuronal networks, neuronal protein accumulation, acceleration of oxidative stress, and alteration of neurofibrillary tangles, and hinders distinctive communicating pathways. Conclusively, alterations of these neurotoxic factors are possibly responsible for the associated neurodegenerative disorders due to the exposure of MPs/NPs. In this review, the hypothesis on MPs/NPs associated with gut microbial dysbiosis has been interlinked to the distinct neurological impairment through the gut-brain axis.

Human milk (HM) is considered the best source of infant nutrition with many benefits for the infant. However, pregnancy changes can lead to increased stress in some women, which might affect HM composition. Although studies have demonstrated a link between maternal psychopathology and child development, it remains unclear how maternal psychobiological changes can be intergenerationally transmitted. We aimed to investigate the associations of maternal stress, depressive symptoms, and anxiety symptoms with the HM microbiome; to analyze these parameters in relation to HM glucocorticoid concentrations; and to explore the influence of HM glucocorticoids on HM bacterial composition.

One hundred women completed psychological questionnaires (e.g., EPDS, STAI, GAS) at 34-36 weeks' gestation and in the early postpartum period and provided saliva at 34-36 and 38 weeks' gestation. HM samples were collected in the early postpartum. Microbiota were analyzed using 16S rRNA amplicon sequencing.

Birth anxiety was negatively correlated with Alphaproteobacteria (τ = -0.20, FDR = 0.01), whereas in the postpartum period, anxiety symptoms were negatively correlated with different taxa. The sum of postpartum-related symptoms was linked to lower Propionibacteriales. Salivary cortisol AUCg at 34-36 weeks was negatively correlated with Stenotrophomonas (τ = -0.24, FDR = 0.05), whereas HM cortisol was positively correlated with Streptococcus mitis (τ = 0.26, FDR = 0.03) and Gemella haemolysans (τ = 0.24, FDR = 0.02). No associations emerged between psychobiological parameters and HM glucocorticoids.

Higher perinatal psychological symptoms and prenatal salivary cortisol AUCg were associated with lower relative abundances of different bacteria, whereas higher HM cortisol was linked to higher Gemella and Streptococcus. These findings suggest a negative association between high maternal psychobiological symptoms and relative abundances of the milk microbiota.

Mental health is a serious issue, with mental health disorders affecting millions of people globally. Gut microbiota has received considerable attention because of its potential role in the pathogenesis of mental health disorders. This systematic review synthesized 15 studies exploring the effects of the gut microbiome on depression, anxiety, schizophrenia, and bipolar disorder, with qualitative and quantitative insights. The studies were conducted in different countries and employed various methods including 16S rRNA sequencing and metagenomic analysis with sample sizes varying from 50 to 600. Some of the key findings were that depression was associated with reduced microbial diversity and high levels of Firmicutes, and anxiety was associated with low levels of short-chain fatty acid (SCFA)-producing bacteria and high levels of Proteobacteria. Schizophrenia was related to endotoxemia and a reduction in the Lactobacillus count whereas bipolar disorder displayed a shift in the Firmicutes/Bacteroidetes ratio. Of interest, probiotics and dietary changes were as effective as drug treatment leading to symptom alleviation in many patients. It was found that depression was linked to less diverse gut bacteria while anxiety was associated with an increase in inflammatory bacteria. People with bipolar disorder were also found to have different gut bacteria patterns. This review also emphasizes the importance of the gut microbiota in the pathophysiology of mental disorders and the promising value of targeting microbiomes in pharmacological treatment approaches.

A growing number of studies have highlighted the significance of human gut microbiota (GM) as a potential target for osteoporosis. In this review, we discuss the effect of GM to bone metabolism focusing on two aspects: the local alterations of the human gut permeability that modify how the GM interact with the gut-bone axis (e.g., intestinal leakage, nutrient absorption), and the alterations of the GM itself (e.g., changes in microbiota metabolites, immune secretion, hormones) that modify the events of the gut-bone axis. We then classify these changes as possible therapeutic targets of bone metabolism and highlight some associated promising microbiome-based therapies. We also extend our discussions into combinatorial treatments that incorporate conservative treatments, such as exercise. We anticipate our review can provide an overview of the current pathophysiological and therapeutic paradigms of the gut-bone axis, as well as the prospects of ongoing clinical trials for readers to gain further insights into better microbiome-based treatments to osteoporosis and other bone-degenerative diseases. The translational potential of this article: This paper reviewed the potential links between gut microbiota and osteoporosis, as well as the prospective therapeutic avenues targeting gut microbiota for osteoporosis management, presenting a thorough and comprehensive literature review.

Gut microbiota is generally considered to play an important role in host health due to its extensive immunomodulatory activities. Th17 and Treg cells are two important CD4+ T cell subsets involved in immune regulation, and their imbalance is closely tied to many immune diseases. Recently, abundant researches have highlighted the importance of gut microbiota in supporting intestinal and extraintestinal immunity through the balance of Th17 and Treg cells. Here, we presented a comprehensive review of these findings. This review first provided an overview of gut microbiota, along with Th17/Treg cell differentiation and cytokine production. Subsequently, the review summarized the regulatory effects of gut microbiota (in terms of species, components, and metabolites) on the Th17/Treg cell balance in the local intestines and extraintestinal organs, such as lung, liver, brain, kidney, and bone. Specifically, the Th17 and Treg cells that can be modulated by gut microbiota originate not only from the gut and extraintestinal organs, but also from peripheral blood and spleen. Then, the microbial therapeutics, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), were also reviewed because of their therapeutic potentials in addressing intestinal and extraintestinal diseases via the Th17/Treg axis. Finally, the review discussed the clinical applications and future study prospects of microbial therapeutics by targeting the Th17/Treg cell balance. In conclusion, this review focused on elucidating the regulatory effects of gut microbiota in balancing Th17/Treg cells to maintain intestinal and extraintestinal immune homeostasis, contributing to the further development and promotion of microbial therapeutics.

Studies have shown correlations between gut microbiota and neurocognitive function, but little was known about the early postnatal gut microbiota and intraventricular hemorrhage (IVH). We aimed to explore the characteristics of gut microbiota in premature infants and their relationship with IVH, further exploring potential therapeutic targets.

Premature infants delivered at Peking University First Hospital from February 2023 to August 2023 were recruited as a cohort. Feces samples were collected on postnatal days 1, 3, and 5. Premature infants were divided into normal, mild IVH, and severe IVH groups based on cranial ultrasound. 16S rRNA amplicon sequencing technology was used to determine the fecal microbiota, and the results were analyzed.

Thirty-eight premature infants were enrolled. There was a significant difference in alpha and beta diversity among the three groups. The relative abundance of E. coli and A. muciniphila was different among the three groups. Further random forest analysis indicated that S. lutetiensis, L. mirabilis, and N. macacae can effectively distinguish premature infants with IVH. Finally, the phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) functional gene analysis predicted significant differences in energy metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and membrane transport between normal and severe IVH groups.

The gut microbiota in the early postnatal period of premature infants is closely associated with the IVH status. As age increases, the differences in gut microbiota of premature infants with different degrees of IVH continue to increase, and the trend of changes with severity of IVH becomes more and more obvious. E. coli, A. muciniphila, S. lutetiensis, L. mirabilis, N. macacae, G. haemolysans, and S. oralis can effectively distinguish between IVH infants and normal premature infants. The results indicate that gut microbiota is expected to provide effective therapeutic targets for the diagnosis and treatment of IVH.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that combines genetic and environmental factors. The human microbiota is colonized by permanent or transitory microorganisms, depending on the host and the external factors controlling their permanence. The composition of the gut microbiota (GM) in ASD individuals is notably different from that in controls, which may contribute to the clinical conditions observed in these individuals. This study aimed to indirectly investigate the influence of GM on the gut-brain axis in individuals with ASD and controls by analyzing environmental factors that contribute to the microbiota composition. Two questionnaires were designed to collect data, one for the ASD Group (ASDG) and the other one for the Control Group (CG). The raw data from both questionnaires were collected from 2772 respondents. After triage, answers from 1687 ASD individuals, along with 466 respondents from the CG, were analyzed, resulting in a total of 2237 respondents. Our results showed that gastrointestinal problems (GP) escalate as individuals age and become more prominent in ASD individuals. In contrast, feeding problems (FP) did not appear to escalate in either group as individuals aged, even though the FP decreased in the CG. ANOVA revealed significant differences in breastfeeding status compared to GPs among preterm control individuals born via cesarean section (p-value = 0.027). The mean values of GP for breastfed and nonbreastfed individuals, for ASDG (0.257; 0.268) and CG (0.105; 0.248), highlighted the differences in breastfeeding effects on GP for the study groups. The use of antibiotics during pregnancy seemed to be significant for GPs in the ASDG only for breastfed individuals (p-value <0.001), but not in the CG group. In conclusion, variables such as mode of delivery, FPs, type of birth, and length of breastfeeding do not seem to be determining factors for GP in the ASDG but are relevant for the CG. However, for ASDG individuals whose mothers took antibiotics during pregnancy, breastfeeding may act as a protective factor, as maternal antibiotic administration during pregnancy seems to aggravate GP-values across the ages of the participants. Considering GP as a proxy for GM and recognizing the importance of GM composition for central nervous system (CNS) function, it appears that in individuals with ASD, GM seems to be more dependent on other factors, which might be linked to the genetic background of each one. These findings suggest that future studies of the gut-brain axis in individuals with ASD might consider the individual's genetic background, environmental factors, and GM.

The tryptophan-kynurenine (KYN) pathway has long been recognized for its essential role in generating metabolites that influence various physiological processes. Traditionally, these metabolites have been categorized into distinct, often opposing groups, such as pro-oxidant versus antioxidant, excitotoxic/neurotoxic versus neuroprotective. This dichotomous framework has shaped much of the research on conditions like neurodegenerative and neuropsychiatric disorders, as well as cancer, where metabolic imbalances are a key feature. The effects are significantly influenced by various factors, including the concentration of metabolites and the particular cellular milieu in which they are generated. A molecule that acts as neuroprotective at low concentrations may exhibit neurotoxic effects at elevated levels. The oxidative equilibrium of the surrounding environment can alter the function of KYN from an antioxidant to a pro-oxidant. This narrative review offers a comprehensive examination and analysis of the contemporary understanding of KYN metabolites, emphasizing their multifaceted biological functions and their relevance in numerous physiological and pathological processes. This underscores the pressing necessity for a paradigm shift in the comprehension of KYN metabolism. Understanding the context-dependent roles of KYN metabolites is vital for novel therapies in conditions like Alzheimer's disease, multiple sclerosis, and cancer. Comprehensive pathway modulation, including balancing inflammatory signals and enzyme regulation, offers promising avenues for targeted, effective treatments.

The gut microbiota plays a fundamental role in the host's energy metabolism and the development of metabolic diseases such as arterial hypertension, insulin resistance, and atherosclerosis. Our study aimed to investigate the potential role of the gut microbiota in arterial hypertension among individuals of the Kazakh population without insulin resistance. 16S rRNA gene sequencing of faecal samples from 197 Kazakh subjects was performed. Preliminary binary comparisons of the faecal microbiota composition depending on the presence of arterial hypertension and insulin resistance revealed statistically significant differences in the abundance of the phylum Firmicutes. Logistic regression analysis showed that only the phylum Firmicutes influenced hypertension risk in individuals without insulin resistance after adjusting for age, sex, BMI, fasting glucose, triglycerides, and triglyceride-glucose index. The higher the abundance of the phylum Firmicutes in faeces, the greater the risk of arterial hypertension (OR = 1.064 [95% CI 1.005-1.125]). Correlation analysis revealed a negative association between the abundance of the phylum Firmicutes and the triglyceride-glucose index, primarily driven by triglyceride levels. These findings suggest the potential role of the gut microbiota, especially the phylum Firmicutes, in the development of hypertension in individuals without insulin resistance.

Many probiotics produce functional lipids with health-promoting properties, such as short-chain fatty acids, linoleic acid and omega-3 fatty acids. They have been shown to maintain gut health, strengthen the intestinal barrier, and have anti-inflammatory and antioxidant effects. In this article, we provide an up-to-date review of the various functional lipids produced by probiotics. These probiotics can be incorporated into foods, supplements, or pharmaceuticals to produce these functional lipids in the human colon, or they can be used in industrial biotechnology processes to generate functional lipids, which are then isolated and used as ingredients. We then highlight the different physiological functions for which they may be beneficial to human health, in addition to discussing some of the challenges of incorporating probiotics into commercial products and some potential solutions to address these challenges. Finally, we highlight the importance of testing the efficacy and safety of the new generation of probiotic-enhanced products, as well as the great potential for the marketization of related products.

Rare earth elements (REEs) are widely used in plenty of fields. REEs have significant neurotoxicity and it may adversely affect the development of cognitive. For example, neodymium will causing neurological damage through penetrate the blood-brain barrier (BBB). However, whether it disrupts the balance of brain-gut axis (BGA) crosstalk and affects the intestinal microecology disorder of host is still unclear. This study investigated the neural damage on children caused by maternal exposure to Neodymium oxide (Nd2O3) during pregnancy, and its involved mechanism of BGA injury.

We used rat model to investigated the mechanisms of the offspring's neural damage that Nd2O3 exposure in pregnancy. To verify the neural damage of offspring rats, we examed BBB-related factors, such like glutamate and ROS levels in brain tissue, behavioral tests, hippocampal and cortical damage, as well as changes in gut microbiota, intestinal mucosal barrier, and SCFAs in the intestine. Also, we observed some specific indicators of intestinal immune barrier function and gut nerve-related indicators.

Maternal Nd2O3 exposure reduced the content of offspring tight junction proteins, increased BBB permeability, leading to Nd accumulation and brain tissue inflammation, affecting offspring's neural development and weakening their spatial learning ability. Nd2O3 also disrupted BBB integrity by regulating SCFAs and BGA. Probiotic intervention in the offspring rats exposed to 2% Nd2O3 showed significant recovery of inflammation in both brain and colon tissues, and reduced BBB permeability.

Maternal exposure to Nd2O3 affects the offspring's BGA, targeting brain and colon tissues, increasing BBB permeability, affecting neural development, causing damage to the intestinal mucosa, and impacting children's gut development. Probiotics can alleviate these effects. These findings provide valuable insights into understanding the neurodevelopmental and intestinal developmental toxicity of Nd2O3 and its prevention and treatment. It also calls for a comprehensive assessment of the health risks of susceptible populations to Nd2O3, such as pregnant women. It may providing theoretical basis for preventing and controlling neodymium-induced harm in children by examing the repair mechanism of the damage through probiotic intervention.